The objective of this proposal is to determine, at the level of individual neurons, how the nervous system readjusts its effective interconnections to facilitate recovery of function in response to chronic lesions in the CNS. Such striking plasticity has been described for the leech, a favorable model preparation for detailed cellular analysis; two neurally isolated body parts of an operated leech can learn to coordinate their independent swimming movement within a few months without regeneration of the nerve cord. The ability to discover modified connectivity may be enhanced as a result of progress in the development of optical methods for monitoring neuronal activity. We were able to record action potentials and large synaptic potentials from many individual CNS neurons simultaneously: Using this technique it has been possible to monitor simultaneously, activity of 50-100 neurons in a simple invertebrate CNS similar to the leech. This capability facilitates fast determination of partial wiring diagrams, for example, mapping of monosynaptic connections made by a single neuron with the other neurons in the ganglion, can be done in a single experiment, which may last a few minutes. The new method, combined with electrophysiological approaches, will be used to evaluate the degree of variability and specificity of interconnections among the neurons controlling swimming behavior and between sensory neurons and those neurons. Then, we shall study the dynamics, and the specificity of reforming connections during regeneration, or during reorganization in response to chronic lesions which are known to impair swimming, or in response to in situ elimination of single cells.